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Two experiments ( \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $N=116$ \\end{document} ) explored the effects of evaluative conditioning on mature brands. Explicit attitudes for mature brands were unaffected by evaluative conditioning. Experiment 1 showed, however, that evaluative conditioning changed implicit attitudes toward Coke and Pepsi. This occurred only for participants who initially had no strong preference for either brand. Contingency awareness was not necessary to change implicit brand attitudes. Experiment 2 showed that brand choice was related to the altered implicit attitudes, but only when choice was made under cognitive load. Implications of these data for evaluative conditioning specifically, and for consumer research in general, are considered.

Key Points Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification in which ADP-ribose units are added to Glu, Asp and Lys residues of target (or acceptor) proteins by members of the poly(ADP-ribose) polymerase (PARP) family. Seventeen PARP family members have been identified on the basis of homology to PARP1, which is the founding member of the PARP family. PARylation is important for cellular signalling pathways, cytoplasmic and nuclear functions and the response to cellular stress. A number of proteins with poly(ADP-ribose) (PAR) degrading activities have been characterized, such as the endo- and exoglycohydrolase poly(ADP-ribose) glycohydrolase (PARG). PARG promotes the rapid catabolic destruction of PAR almost immediately after synthesis, thus allowing temporal control of PAR functions. Recognition of and binding to PAR occurs through four distinct protein modules: PAR-binding motifs (PBMs), PAR-binding zinc-finger (PBZ) domains, macrodomain folds and WWE domains. Some of these domains are found in PARPs themselves. New evidence has shown that the activation and destruction of PAR modifications can alter protein substrate specificity, localization and stability, and these findings implicate PARPs as a promising target for therapeutic intervention in human disease. The key mechanisms by which PARylation regulates many cellular responses include the inhibition of protein–protein or protein–DNA interactions, nucleation of protein localization and interaction scaffolds, as well as the regulation of other protein modifications, such as ubiquitylation. The involvement of PARP proteins in DNA damage detection and repair, telomere maintenance, and stress responses and recovery gives hope for the use of PARP inhibition as a means for selective 'next generation' therapies for cancer, as well as stress-related diseases that exhibit pro-inflammatory signatures (for example, cardiovascular diseases, stroke, metabolic disorders, diabetes, and autoimmunity). As such, PARPs have recently been targeted with small molecules in clinical trials for a number of human diseases. Poly(ADP-ribosyl)ation (PARylation) is a dynamic protein modification, the control of which is important for diverse cell biological processes and normal physiology. Common mechanistic themes are being characterized by which PARylation alters the functions of target proteins, and the PAR-binding modules that mediate this. Poly(ADP-ribose) polymerases (PARPs) are enzymes that transfer ADP-ribose groups to target proteins and thereby affect various nuclear and cytoplasmic processes. The activity of PARP family members, such as PARP1 and PARP2, is tied to cellular signalling pathways, and through poly(ADP-ribosyl)ation (PARylation) they ultimately promote changes in gene expression, RNA and protein abundance, and the location and activity of proteins that mediate signalling responses. PARPs act in a complex response network that is driven by the cellular, molecular and chemical biology of poly(ADP-ribose) (PAR). This PAR-dependent response network is crucial for a broad array of physiological and pathological responses and thus is a good target for chemical therapeutics for several diseases.

Poly[adenosine diphosphate (ADP)—ribose] polymerases (PARPs) are a family of enzymes that modulate diverse biological processes through covalent transfer of ADP-ribose from the oxidized form of nicotinamide adenine dinucleotide (NAD⁺) onto substrate proteins. Here we report a robust NAD⁺ analog—sensitive approach for PARPs, which allows PARP-specific ADP-ribosylation of substrates that is suitable for subsequent coppercatalyzed azide-alkyne cycloaddition reactions. Using this approach, we mapped hundreds of sites of ADP-ribosylation for PARPs 1, 2, and 3 across the proteome, as well as thousands of PARP-1—mediated ADP-ribosylation sites across the genome. We found that PARP-1 ADP-ribosylates and inhibits negative elongation factor (NELF), a protein complex that regulates promoter-proximal pausing by RNA polymerase II (Pol II). Depletion or inhibition of PARP-1 or mutation of the ADP-ribosylation sites on NELF-E promotes Pol II pausing, providing a clear functional link between PARP-1, ADP-ribosylation, and NELF. This analog-sensitive approach should be broadly applicable across the PARP family and has the potential to illuminate the ADP-ribosylated proteome and the molecular mechanisms used by individual PARPs to mediate their responses to cellular signals.

Nuclear DNA in eukaryotes is wrapped around histone proteins to form nucleosomes on a chromatin fiber. Dynamic folding of the chromatin fiber into loops and variations in the degree of chromatin compaction regulate essential processes such as transcription, recombination, and mitotic chromosome segregation. Our understanding of the physical properties that allow chromatin to be dynamically remodeled even in highly compacted states is limited. Previously, we reported that chromatin has an intrinsic capacity to phase separate and form dynamic liquid-like condensates, which can be regulated by cellular factors [B. A. Gibson et al., Cell 179, 470–484.e421 (2019)]. Recent contradictory reports claim that a specific set of solution conditions is required for fluidity in condensates that would otherwise be solid [J. C. Hansen, K. Maeshima, M. J. Hendzel, Epigenetics Chromatin 14, 50 (2021); H. Strickfaden et al., Cell 183, 1772–1784.e1713 (2020)]. We sought to resolve these discrepancies, as our ability to translate with confidence these biophysical observations to cells requires their precise characterization. Moreover, whether chromatin assemblies are dynamic or static affects how processes such as transcription, loop extrusion, and remodeling will engage them inside cells. Here, we show in diverse conditions and without specific buffering components that chromatin fragments form phase separated fluids in vitro. We also explore how sample preparation and imaging affect the experimental observation of chromatin condensate dynamics. Last, we describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained chromatin movement observed in cells.

Dividing eukaryotic cells package extremely long chromosomal DNA molecules into discrete bodies to enable microtubule-mediated transport of one genome copy to each of the newly forming daughter cells 1 – 3 . Assembly of mitotic chromosomes involves DNA looping by condensin 4 – 8 and chromatin compaction by global histone deacetylation 9 – 13 . Although condensin confers mechanical resistance to spindle pulling forces 14 – 16 , it is not known how histone deacetylation affects material properties and, as a consequence, segregation mechanics of mitotic chromosomes. Here we show how global histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division. Deacetylation-mediated compaction of chromatin forms a structure dense in negative charge and allows mitotic chromosomes to resist perforation by microtubules as they are pushed to the metaphase plate. By contrast, hyperacetylated mitotic chromosomes lack a defined surface boundary, are frequently perforated by microtubules and are prone to missegregation. Our study highlights the different contributions of DNA loop formation and chromatin phase separation to genome segregation in dividing cells. Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.

Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization in vivo. Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation. We show that as DNA linkers extend from 25 bp to 30 bp, as exemplars of 10 N + 5 and 10 N (integer N) bp lengths, chromatin condensates become less thermodynamically stable and nucleosome mobility increases. Simulations reveal that this is due to trade-offs between inter- and intramolecular nucleosome stacking, favored by rigid 10 N + 5 and 10 N bp linkers, respectively. A remodeler can induce or inhibit phase separation by moving nucleosomes, changing the balance between intra- and intermolecular stacking. The intrinsic phase separation capacity of chromatin enables fine tuning of compaction and dynamics, likely contributing to heterogeneous chromatin organization in vivo. Internucleosomal linker length alters the stability and dynamics of chromatin condensates by shifting the balance between inter- and intramolecular interactions. Further, by changing the linker lengths, a remodeler can induce or suppress chromatin phase separation.

PARP-7 (TiPARP) is a mono(ADP-ribosyl) transferase whose protein substrates and biological activities are poorly understood. We observed that PARP7 mRNA levels are lower in ovarian cancer patient samples compared to non-cancerous tissue, but PARP-7 protein nonetheless contributes to several cancer-related biological endpoints in ovarian cancer cells (e.g. growth, migration). Global gene expression analyses in ovarian cancer cells subjected to PARP-7 depletion indicate biological roles for PARP-7 in cell-cell adhesion and gene regulation. To identify the MARylated substrates of PARP-7 in ovarian cancer cells, we developed an NAD + analog-sensitive approach, which we coupled with mass spectrometry to identify the PARP-7 ADP-ribosylated proteome in ovarian cancer cells, including cell-cell adhesion and cytoskeletal proteins. Specifically, we found that PARP-7 MARylates α-tubulin to promote microtubule instability, which may regulate ovarian cancer cell growth and motility. In sum, we identified an extensive PARP-7 ADP-ribosylated proteome with important roles in cancer-related cellular phenotypes. Cancer is a complex illness where changes inside healthy cells causes them to grow and reproduce rapidly. Specialized proteins called enzymes – which regulate chemical reactions in the cell – often help cancer develop and spread through the body. One such enzyme called PARP-7 labels other proteins by attaching a chemical group which changes their behavior. However, it was unknown which proteins PARP-7 modifies and how this tag alters the actions of these proteins. To investigate this, Parsons, Challa, Gibson et al. developed a method to find and identify the proteins labelled by PARP-7 in ovarian cancer cells taken from patients and cultured in the laboratory. This revealed that PARP-7 labels hundreds of different proteins, including adhesion proteins which affect the connections between cells and cytoskeletal proteins which regulate a cell’s shape and how it moves. One of the cytoskeletal proteins modified by PARP-7 is α-tubulin, which joins together with other tubulins to form long, tube-like structures known as microtubules. Parsons et al. found that when α-tubulin is labelled by PARP-7, it creates unstable microtubules that alter how the cancer cells grow and move. They discovered that depleting PARP-7 or mutating the sites where it modifies α-tubulin increased the stability of microtubules and slowed the growth of ovarian cancer cells. Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the United States. A new drug which suppresses the activity of PARP-7 has recently been developed, and this drug could potentially be used to treat ovarian cancer patients with high levels of PARP-7. Clinical trials are ongoing to see how this drug affects the behavior of cancer cells in patients.

Although counting problems are easy to state and provide rich, accessible problem-solving situations, there is much evidence that students struggle with solving counting problems correctly. With combinatorics (and the study of counting problems) becoming increasingly prevalent in K–12 and undergraduate curricula, there is a need for researchers to identify potentially significant factors that might have an effect on student success as they solve counting problems. We tested one such factor among undergraduate students—their systematic listing of what they were trying to count. We argue that even creating partial lists of the set of outcomes led to significant improvements in performance in students' success on problems, implying that systematic listing may be worthwhile for students to engage in as they learn to count. Our findings suggest that more needs to be done to refine instructional interventions that facilitate listing. We discuss these findings and suggest avenues for further research.